4-87611030-AGTGTGTGTGTGT-AGTGTGT

Variant names:

• chr4-87611030-AGTGTGT-A
• rs33940466
• NM_014208.3:c.51+99_51+104delTGTGTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014208.3(DSPP):​c.51+99_51+104delTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 821,072 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

Genes affected

DSPP (HGNC:3054): (dentin sialophosphoprotein) This gene encodes a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of proteins. The encoded preproprotein is secreted by odontoblasts and proteolytically processed to generate two principal proteins of the dentin extracellular matrix of the tooth, dentin sialoprotein and dentin phosphoprotein. These two protein products may play distinct but related roles in dentin mineralization. Mutations in this gene are associated with dentinogenesis imperfecta and dentin dysplasia. This gene is present in a gene cluster on chromosome 4. Allelic differences due to repeat polymorphisms have been found for this gene. [provided by RefSeq, Jan 2016]

ENSG00000249001 (HGNC:58144):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00174 (254/145682) while in subpopulation SAS AF= 0.00665 (30/4508). AF 95% confidence interval is 0.00479. There are 1 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 254 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+99_51+104delTGTGTG		intron_variant	Intron 2 of 4	ENST00000651931.1	NP_055023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1	c.51+72_51+77delGTGTGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42503_323-42498delACACAC		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 249 AN: 145584 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00100

Gnomad SAS AF: 0.00665

Gnomad FIN AF: 0.000105

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.000541

Gnomad OTH AF: 0.00200

GnomAD4 exome AF: 0.00182 AC: 1226 AN: 675390 Hom.: 0 AF XY: 0.00201 AC XY: 729 AN XY: 362014

Gnomad4 AFR exome AF: 0.00639

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.000444

Gnomad4 EAS exome AF: 0.00175

Gnomad4 SAS exome AF: 0.00551

Gnomad4 FIN exome AF: 0.000516

Gnomad4 NFE exome AF: 0.00129

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00174 AC: 254 AN: 145682 Hom.: 1 Cov.: 0 AF XY: 0.00163 AC XY: 115 AN XY: 70610

Gnomad4 AFR AF: 0.00387

Gnomad4 AMR AF: 0.00172

Gnomad4 ASJ AF: 0.000294

Gnomad4 EAS AF: 0.00100

Gnomad4 SAS AF: 0.00665

Gnomad4 FIN AF: 0.000105

Gnomad4 NFE AF: 0.000541

Gnomad4 OTH AF: 0.00198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs33940466; hg19: chr4-88532182;